Process for producing aromatic aldehyde

ABSTRACT

A process for producing an aromatic aldehyde compound represented by a general formula (3):  
                 
 
(wherein R′ and n are as defined below), which comprises reacting a benzyl compound represented by a general formula (1):  
                 
(wherein R may represents hydrogen atom, n represents an integer of 1 to 6, and R′ may be the same or different and represent a hydrogen atom or an alkyl gorup, an alkyl group or a phenyl group which may have a substituent) with an oxy-compound of bromine represented by the formula (2): 
 
MBrO m   (2) 
(wherein M represents a hydrogen atom or a metal atom, and m represents an integer of 1 to 3) in the presence of an acid catalyst. According to this method, an aromatic aldehyde compound can be produced in high selectivity by a simple operation without using an expensive catalyst or transition metal.

TECHNICAL FIELD

The present invention relates to a process for producing a correspondingaromatic aldehyde compound by oxidizing a benzyl alcohol compound or abenzyl ether compound.

BACKGROUND ART

As a process for producing a corresponding aromatic aldehyde compound byoxidizing a benzyl alcohol compound, there have hitherto been knownvarious methods for oxidation reaction, inclusive of: e.g., oxidationwith chromic acid, oxidation with active manganese dioxide, oxidationwith dimethyl sulfoxide typified by Swern oxidation, oxidation with anoxoammonium salt compound such as 2,2,6,6-tetramethylpiperidinooxy freeradical (TEMPO), and oxidation with a transition metal catalyst such asruthenium catalyst [JIKKEN KAGAKU KOZA (Experimental Chemistry Course),edited by The Chemical Society of Japan, Organic SynthesisIII-Aldehyde•Ketone•Quinone-, 4th edition, MARUZEN Co., Ltd., 1991, Vol.21, pp. 1-20].

However, in the method for oxidation with chromic acid or activemanganese dioxide among the above-mentioned conventional methods, theresidual harmful metal compound must be treated after the completion ofthe reaction. In the method for oxidation with dimethyl sulfoxide, anequivalent or more of an activating agent such asdicyclohexylcarbodiimide (DCC) or acid chloride must be used.Furthermore, in the method for oxidation with an oxoammonium saltcompound and the method for oxidation with a transition metal catalyst,an expensive catalyst must be used.

Also, there has been known oxidation with hydrogen peroxide water in thepresence of a catalytic amount of sodium tungstate [Tetrahedron Lett.,Vo. 39, pp. 7549 (1998)]. However, a problem such as poor reactivity hasstill been unsolved, with respect to a compound having a substituentsuch as nitro group.

Furthermore, there has been known a method in which one equivalent ofsodium bromate is used in an acetonitrile-water solvent mixture in thepresence of 1.5 equivalents of ammonium chloride [J. Chem. Research(s),pp. 100 (1998)]. However, the use of a stoichiometric three-fold amountof an oxidizing agent and a treatment of one equivalent of sodiumbromide as a waste are not preferable from industrial point of view.

DISCLOSURE OF THE INVENTION

An object of the present invention is to provide a novel process forproducing an aromatic aldehyde compound in which the above-mentionedproblem encountered in the prior art has been solved.

Another object of the present invention is to provide a novel processfor producing a corresponding aromatic aldehyde compound by oxidizing abenzyl alcohol compound or a benzyl ether compound.

As a result of earnest study, the present inventor has surprisinglyfound that it is remarkably effective in solving the above-mentionedproblem to react a benzyl alcohol compound or a benzyl ether compoundwith a small amount approximately corresponding to the stoichiometricamount (a small amount less than the stoichiometric amount, in somecases) of oxy-compound of bromine. The present invention has beencompleted based on such a discovery.

BEST MODES FOR CARRYING OUT THE INVENTION

The present invention will now be described in detail with reference tothe accompanying drawing, as desired. In the following description,parts and percentages, which indicate a quantitative ratio, are byweight unless otherwise specifically noted.

The present invention includes, e.g., the following embodiments [1] to[11].

[1] A process for producing an aromatic aldehyde compound represented bya general formula (3):

(wherein R′ and n are as defined below), comprising: reacting a benzylcompound represented by a general formula (1):

(wherein R represents a hydrogen atom or an alkyl group, n represents aninteger of 1 to 6, and R′ may be the same or different and eachindependently represents a hydrogen atom, an alkyl group, a hydroxylgroup, an alkoxy group, a hydroxyalkyl group, an alkoxyalkyl group, ahaloalkyl group, a carboxyl group or a metal salt thereof, analkoxycarbonyl group, a halogen atom, a nitro group, an amino group, analkylamino group, an alkylcarbonylamino group, a cyano group, a formylgroup, an alkylcarbonyl group, or a phenyl group which may have asubstituent), with an oxy-compound of bromine represented by a generalformula (2):MBrO_(m)  (2)

(wherein M represents a hydrogen atom or a metal atom, and m representsan integer of 1 to 3) in the presence of an acid catalyst.

[2] A process for producing an aromatic aldehyde compound according to[1], wherein, in the benzyl compound represented by a general formula(1), all R′(s) are hydrogen atoms or at least one of R′(s) is anelectron-withdrawing group.

[3] A process for producing an aromatic aldehyde compound according to[1], wherein, in the benzyl compound represented by a general formula(1), all R′(s) are hydrogen atoms or at least one of R′(s) is at leastone of a nitro group, a chloro group and a hydroxymethyl group.

[4] A process for producing an aromatic aldehyde compound according toany one of claims 1 to 3, wherein the oxy-compound of brominerepresented by a general formula (2) is bromic acid, bromate or bromite.

[5] A process for producing an aromatic aldehyde compound according toany one of [1] to [3], wherein the oxy-compound of bromine representedby a general formula (2) is bromate.

[6] A process for producing an aromatic aldehyde compound according toany one of [1] to [3], wherein the acid catalyst is an organiccarboxylic acid.

[7] A process for producing an aromatic aldehyde compound according toany one of [1] to [3], wherein the acid catalyst is acetic acid.

[8] A process for producing an aromatic aldehyde compound according toany one of [1] to [3], wherein the oxy-compound of bromine representedby a general formula (2) is bromate or bromite and the acid catalyst isan organic carboxylic acid.

[9] A process for producing an aromatic aldehyde compound according toany one of [1] to [3], wherein the oxy-compound of bromine representedby a general formula (2) is bromate and the acid catalyst is an organiccarboxylic acid.

[10] A process for producing an aromatic aldehyde compound according toany one of [1] to [3], wherein the oxy-compound of bromine representedby a general formula (2) is bromate or bromite and the acid catalyst isacetic acid.

[11] A process for producing an aromatic aldehyde compound according toany one of [1] to [3], wherein the oxy-compound of bromine representedby a general formula (2) is bromate and the acid catalyst is aceticacid.

(Process for Producing Aromatic Aldehyde Compound)

The process according to the present invention is a process forproducing an aromatic aldehyde compound represented by a general formula(3) by reacting a benzyl compound represented by a general formula (1)with a oxy-compound of bromine represented by a general formula (2) inthe presence of an acid catalyst.

(Benzyl Compound)

First, the benzyl compound represented by a general formula (1)(hereinafter, sometimes referred to as “raw material benzyl compound”)used as a raw material for the process according to the presentinvention will be described.

R in a general formula (1) represents a hydrogen atom; or a linear orbranched C₁-C₆ alkyl group such as methyl group, ethyl group, n-propylgroup, isopropyl group, n-butyl group, sec-butyl group, t-butyl group,n-pentyl group, or n-hexyl group. In view of reactivity, R maypreferably be a hydrogen atom or an alkyl group having 1 to 3 carbonatoms.

R′ in a general formula (1) may be the same or different and eachindependently represents a hydrogen atom; a linear or branched C₁-C₆alkyl group having 1 to 6 carbon atoms (hereinafter, when a group has 1to 6 carbon atoms, the group is abbreviated to a “C₁-C₆ group”) such asmethyl group, ethyl group, n-propyl group, isopropyl group, n-butylgroup, sec-butyl group, t-butyl group, n-pentyl group, or an n-hexylgroup; a hydroxyl group; a linear or branched C₁-C₆ alkoxy group such asmethoxy group, ethoxy group, n-propoxy group, or isopropoxy group; alinear or branched C₁-C₆ hydroxyalkyl group such as hydroxymethyl groupor hydroxyethyl group; a linear or branched (C₁-C₆ alkoxy)-(C₁-C₆ alkyl)group such as methoxymethyl group, methoxyethyl group, or ethoxyethylgroup; a linear or branched C₁-C₆ haloalkyl group such as fluoromethylgroup, difluoromethyl group, or trifluoromethyl group; a carboxyl groupor a metal salt thereof; a linear or branched (C₁-C₆ alkoxy)carbonylgroup such as methoxycarbonyl group or ethoxycarbonyl group; a halogenatom such as bromine, chlorine, fluorine, or iodoine atom; nitro group;an amino group; a linear or branched mono or di(C₁-C₆ alkyl)amino groupsuch as methylamino group, dimethylamino group, ethylamino group, ordiethylamino group; a linear or branched (C₁-C₆ alkyl)carbonylaminogroup such as acetylamino group, propionylamino group, or butyrylaminogroup; a cyano group; a formyl group; a linear or branched (C₁-C₆alkyl)carbonyl group such as methylcarbonyl group or ethylcarbonylgroup; or a phenyl group (the phenyl group may have a substituent, forexample, a linear or branched C₁-C₆ alkyl group such as methyl group,ethyl group, n-propyl group, isopropyl group, n-butyl group, sec-butylgroup, t-butyl group, n-pentyl group, or n-hexyl group; a hydroxylgroup; a linear or branched C₁-C₆ alkoxy group such as methoxy group,ethoxy group, n-propoxy group, or isopropoxy group; a linear or branchedC₁-C₆ hydroxyalkyl group such as hydroxymethyl group or hydroxyethylgroup; a linear or branched (C₁-C₆ alkoxy)-(C₁-C₆ alkyl) group such asmethoxymethyl group, methoxyethyl group, or ethoxyethyl group; a linearor branched C₁-C₆ haloalkyl group such as fluoromethyl group,difluoromethyl group, or trifluoromethyl group; a carboxyl group or ametal salt thereof; a linear or branched (C₁-C₆ alkoxy)carbonyl groupsuch as methoxycarbonyl group or ethoxycarbonyl group; a halogen atomsuch as bromine, chlorine, fluorine or iodine atom; a nitro group; anamino group; a linear or branched mono or di(C₁-C₆ alkyl)amino groupsuch as methylamino group, dimethylamino group, ethylamino group, ordiethylamino group; a linear or branched C₁-C₆ alkylcarbonylamino groupsuch as acetylamino group, propionylamino group, or butyrylamino group;a cyano group; a formyl group; or a linear or branched (C₁-C₆alkyl)carbonyl group such as methylcarbonyl group or ethylcarbonylgroup).

In view of reactivity, R′ may preferably be a hydrogen atom; or anelectron-withdrawing group such as C₁-C₆ hydroxyalkyl group, (C₁-C₆alkoxy)-(C₁-C₆ alkyl) group, C₁-C₆ haloalkyl group, carboxyl group or ametal salt thereof, (C₁-C₆ alkoxy)carbonyl group, halogen atom, nitrogroup, (C₁-C₆ alkyl)carbonylamino group, cyano group, formyl group, or(C₁-C₆ alkyl)carbonyl group.

Among these substituents, R′ may preferably be a hydrogen atom, a C₁-C₆hydroxyalkyl group, a C₁-C₆ haloalkyl group, a carboxyl group or a metalsalt thereof, a (C₁-C₆ alkoxy)carbonyl group, a halogen atom, a nitrogroup, a cyano group, a formyl group, or a (C₁-C₆ alkyl)carbonyl group,and may be particularly preferably a hydrogen atom, a nitro group, ahalogen atom, or a C₁-C₆ hydroxyalkyl group. Furthermore, good resultsmay be obtained when R′ is a hydrogen atom, a nitro group, a chlorogroup, or a hydroxymethyl group.

n in a general formula (1) represents an integer of 1 to 6. In theprocess according to the present invention, n may preferably be from 1to 3 in view of availability of a raw material and reactivity.

(Specific Examples of Benzyl Compound)

Specific examples of the benzyl compound represented by a generalformula (1) (raw material benzyl compound), which can be used in thisreaction, include benzyl alcohol, methoxymethylbenzene,o-hydroxymethyltoluene, m-hydroxymethyltoluene, p-hydroxymethyltoluene,o-methoxymethyltoluene, m-methoxymethyltoluene, p-methoxymethyltoluene,o-hydroxymethyl phenol, m-hydroxymethyl phenol, p-hydroxymethyl phenol,o-methoxymethyl phenol, m-methoxymethyl phenol, p-methoxymethyl phenol,o-methoxybenzyl alcohol, m-methoxybenzyl alcohol, p-methoxybenzylalcohol, o-methoxymethoxymethylbenzene, m-methoxymethoxymethylbenzene,p-methoxymethoxymethylbenzene, o-xylylene glycol, m-xylylene glycol,p-xylylene glycol, o-xylylene glycol monomethyl ether, m-xylylene glycolmonomethyl ether, p-xylylene glycol monomethyl ether, o-xylylene glycoldimethyl ether, m-xylylene glycol dimethyl ether, p-xylylene glycoldimethyl ether, o-fluoromethylbenzyl alcohol, m-fluoromethyl-benzylalcohol, p-fluoromethyl-benzyl alcohol,o-methoxymethyl-fluoromethylbenzene,m-methoxymethyl-fluoromethylbenzene,p-methoxymethyl-fluoromethylbenzene, o-hydroxymethylbenzoic acid,m-hydroxymethylbenzoic acid, p-hydroxymethylbenzoic acid,o-methoxymethylbenzoic acid, m-methoxymethylbenzoic acid,p-methoxymethylbenzoic acid, methyl o-hydroxymethylbenzoate, methylm-hydroxymethylbenzoate, methyl p-hydroxymethylbenzoate, methylo-methoxymethylbenzoate, methyl m-methoxymethylbenzoate, methylp-methoxymethylbenzoate, o-chlorobenzyl alcohol, m-chlorobenzyl alcohol,p-chlorobenzyl alcohol, o-chlorobenzyl methyl ether, m-chlorobenzylmethyl ether, p-chlorobenzyl methyl ether, o-nitrobenzyl alcohol,m-nitrobenzyl alcohol, p-nitrobenzyl alcohol, o-nitrobenzyl methylether, m-nitrobenzyl methyl ether, p-nitrobenzyl methyl ether,o-hydroxymethylaniline, m-hydroxymethylaniline, p-hydroxymethylaniline,o-methoxymethylaniline, m-methoxymethylaniline, p-methoxymethylaniline,N-methyl-o-hydroxymethylaniline, N-methyl-m-hydroxymethylaniline,N-methyl-p-hydroxymethylaniline, N-methyl-o-methoxymethylaniline,N-methyl-m-methoxymethylaniline, N-methyl-p-methoxymethylaniline,o-hydroxymethylacetoanilide, m-hydroxymethylacetoanilide,p-hydroxymethylacetoanilide, o-methoxymethylacetoanilide,m-methoxymethylacetoanilide, p-methoxymethylacetoanilide, o-cyanobenzylalcohol, m-cyanobenzyl alcohol, p-cyanobenzyl alcohol, o-cyanobenzylmethyl ether, m-cyanobenzyl methyl ether, p-cyanobenzyl methyl ether,o-hydroxymethylbenzaldehyde, m-hydroxymethylbenzaldehyde,p-hydroxymethylbenzaldehyde, o-methoxymethylbenzaldehyde,m-methoxymethylbenzaldehyde, p-methoxymethylbenzaldehyde,o-hydroxymethylacetophenone, m-hydroxymethylacetophenone,p-hydroxymethylacetophenone, o-methoxymethylacetophenone,m-methoxymethylacetophenone, p-methoxymethylacetophenone,2-hydroxymethylbiphenyl, 3-hydroxymethylbiphenyl,4-hydroxymethylbiphenyl, 2-methoxymethylbiphenyl,3-methoxymethylbiphenyl, 4-methoxymethylbiphenyl,4,4′-dihydroxymethylbiphenyl, and 4,4′-dimethoxymethylbiphenyl.

Among these benzyl compounds, a benzyl compound such as benzyl alcohol,o-, m-, or p-nitrobenzyl alcohol, o-, m-, or p-nitrobenzyl methyl ether,o-, m-, or p-chlorobenzyl alcohol, o-, m-, or p-chlorobenzyl methylether, o-, m-, or p-xylene glycol, or o-, m-, or p-xylene glycolmonomethyl ether may preferably be used.

(Process for Producing Benzyl Compound)

The benzyl compound represented by a general formula (1) (raw materialbenzyl compound) is a known compound, or can be produced by a knownmethod (with respect to details of these reactions, see, for example,documents “Justus Liegibs Annalen der Chemie, Vol. 143, pp. 81, 1867”and “Journal of the American Chemical Society, Vo. 46, pp. 967, 1924”.Examples of such a “known method” include a method of hydrolyzing acorresponding benzyl chloride compound as a raw material in water, or amethod of reacting a corresponding benzyl chloride compound with a metalalkoxide such as sodium alkoxide in a suitable organic solvent.

(Oxy-Compound of Bromine)

Subsequently, oxy-compound of bromine represented by a general formula(2) will be described.

M in a general formula (2) represents a hydrogen atom; or a metal atomof alkali metal such as sodium, potassium or lithium, and alkali earthmetal such as magnesium or calcium.

m in a general formula (2) represents an integer of 1 to 3.

Therefore, specific examples of the oxy-compound of bromine representedby a general formula (2), which can be used in this reaction, bromicacid; bromate typified by bromic acid metal salt such as sodium bromate,potassium bromate, or calcium bromate; bromous acid; bromite typified bybromous acid metal salt such as sodium bromite or potassium bromite;hypobromous acid; and hypobromite. These oxy-compounds of bromine canalso be used in the form of a hydrate.

In view of availability, ease of handling and reactivity, bromic acid,bromate and bromite may preferably be used, and bromate may beparticularly preferably used.

These oxy-compound of bromines represented by a general formula (2) areknown compounds.

(Molar Ratio of Oxy-Compound of Bromine)

With respect to a molar ratio of the oxy-compound of bromine representedby a general formula (2) to be used in this reaction, as far as thereaction proceeds, a molar ratio of the oxy-compound of bromine to thebenzyl compound represented by a general formula (1) (raw materialbenzyl compound) is not specifically limited. To suppress the sidereaction, the molar ratio of oxy-compound of bromine represented by ageneral formula (2) may be usually within a range from 0.3 to 0.5 mols,and preferably from 0.33 to 0.4 mols, based on 1 mol of the benzylcompound represented by a general formula (1) (raw material benzylcompound) when m in a general formula (2) is 3. When m in a generalformula (1) is 2, the molar ratio of the oxy-compound of bromine may beusually within a range from 0.45 to 0.75 mols, and preferably from 0.5to 0.6 mols. When m in a general formula (1) is 1, the molar ratio ofthe oxy-compound of bromine may be usually within a range from 0.9 to1.5 mols, and preferably from 1.0 to 1.2 mols.

When the benzyl compound represented by a general formula (1) (rawmaterial benzyl compound) has a plurality of groups —CH₂OR(hydroxymethyl group, alkoxymethyl group) (that is, a raw materialbenzyl compound is a compound of a general formula (1) wherein n is from2 to 6, or a compound wherein R′ is a phenyl group substituted with agroup —CH₂OR, or a compound which may satisfy both requirements), and itis intended to convert all groups —CH₂OR into formyl groups, it isnecessary to use the oxy-compound of bromine in a molar ratio obtainedby multiplying the molar ratio of the oxy-compound of bromine to be usedby the total number of substituents.

When the raw material benzyl compound has a plurality of groups —CH₂OR,as described above, only a portion of a plurality of groups —CH₂OR canbe converted into formyl groups by controlling the molar ratio of theoxy-compound of bromine represented by a general formula (2).

(Acid Catalyst)

This reaction is conducted using an acid catalyst. Examples of the acidcatalyst, which can be used in this reaction, include carboxylic acidsuch as acetic acid, propionic acid, trifluoroacetic acid, fluoroaceticacid, lactic acid, or amino acid; organic acid typified by organicsulfonic acid such as p-toluenesulfonic acid, methanesulfonic acid, orbenzenesulfonic acid; inorganic acid such as hydrochloric acid, sulfuricacid, or phosphoric acid; Lewis acid such as aluminum chloride, borontrifluoride-tetrahydrofuran complex (BF₃-THF complex), or polyphosphoricacid; and solid acid. Among these acids, carboxylic acid such as aceticacid or propionic acid may preferably be used in view of availabilityand ease of handling.

The amount of the acid catalyst to be used in this reaction is notspecifically limited as far as the reaction sufficiently proceeds, butmay be within a range from 0.01 to 100 mols, and preferably from 0.05 to10 mols, based on 1 mol of benzyl compound represented by a generalformula (1) (raw material benzyl compound) in view of the reaction rateand economical efficiency. However, the amount is not limited within theabove range and an excess amount of the acid catalyst can be used whileserving as a solvent described hereinafter.

(Solvent)

This reaction can be sufficiently conducted with or without using asolvent. The solvent which can be used in the reaction is notspecifically limited as far as it does not exert an adverse influence onthe reaction, and examples thereof include carboxylic acid such asacetic acid or propionic acid; water; aromatic hydrocarbons such astoluene, xylene, and chlorobenzene; halogenated aliphatic hydrocarbonssuch as dichloromethane and chloroform; acetate esters such as methylacetate, ethyl acetate, and butyl acetate; aprotic polar solvents suchas dimethyl formamide, dimethyl acetamide, N-methylpyrrolidone,tetramethylurea, hexamethylphosphorictriamide (HMPA), and propylenecarbonate; ether-based solvents such as diethyl ether, tetrahydrofuran,and dioxane; and aliphatic hydrocarbons such as pentane and n-hexane. Inview of solubility of an oxidizing agent and reactivity, carboxylic acidsuch as acetic acid or propionic acid, or water may preferably be used.It may be particularly preferable to use carboxylic acid as the solventbecause it also serves as the acid catalyst. The above-mentionedsolvents can be used alone or used as a solvent mixture in any mixingratio.

The amount of the solvent may be any amount which enables well stirringof the reaction system. In view of the reaction rate, the amount of thesolvent may be usually within a range from 0.05 to 10 L (liter), andpreferably from 0.5 to 2 L, based on 1 mol of the benzyl compoundrepresented by a general formula (1) (raw material benzyl compound).When the solvent has too low polarity, solubility of the oxidizing agentdecreases and thus the reaction does not proceed smoothly. Therefore, itis undesirable.

(Reaction Temperature)

The reaction temperature of this reaction may be within a range from 0°C. to a reflux temperature of the solvent to be used, and preferablyfrom 20 to 100° C.

When this reaction is carried out under high temperature conditions,vigorous heat generation may occur with rapid progress of the reaction.From such a point of view, it may be advantageous to employ a techniquein which the temperature is carefully set to a low temperature, atechnique in which a benzyl compound is added dropwise to the reactionsystem, a technique in which an oxy-compound of bromine is added to thereaction by several portions, and a technique in which a solutionprepared by dissolving an oxy-compound of bromine in a solvent used oran aqueous oxy-compound of bromine solution is added dropwise to thereaction system.

(Reaction Time)

The reaction time of this reaction is not specifically limited, but maypreferably be within a range from 1 to 30 hours, so as to suppress theproduction of by-product.

In this reaction, bromide ions (Br⁻) generated with the progress of thereaction may partially react with a oxy-compound of bromine to generatea small amount of bromine. This bromine may react with the intendedaromatic aldehyde compound produced in the system thereby to cause sidereaction which can cause oxidation of the corresponding carboxylic acid.From such a point of view, the reaction may preferably be conductedunder mild reaction conditions so as to prevent the generation ofbromine if possible.

(Aromatic Aldehyde Compound)

After the completion of the reaction, the intended aromatic aldehydecompound can be isolated form the reaction mixture by a conventionalmethod. Examples of such a “conventional method” include a method ofdistilling the reaction mixture and optionally rectifying the mixture,or a method of filtrating an intended product in the form of solid andoptionally recrystallizing the product.

According to this reaction, an aromatic aldehyde compound represented bya general formula (3) is produced in high selectivity without causingexcess oxidation reaction in which the oxidation stage of the productproceeds to produce a carboxylic acid compound. The resulting aromaticaldehyde compound represented by a general formula (3) is a compoundwhich is useful as an intermediate of a drug and a agriculturalchemical.

In the present invention, if a GC area to a carboxylic acid compoundproduced as by-product is 1, the intended aromatic aldehyde can beobtained in a GC area ratio of at least 20 or more, usually 45 or more,preferably 90 or more, and particularly preferably 99 or more.

EXAMPLES

The process for producing a compound of the present invention will nowbe described in detail by way of examples, but the present invention isnot limited to the following examples.

Example 1 (An Embodiment of the Invention Described in the AboveEmbodiment [1]): Production of Benzaldehyde

Into a 50 ml three-necked flask equipped with a magnetic stirrer, areflux condenser and a thermometer, 4.32 g (40 mmols) of benzyl alcohol,2.0 g (13.5 mmols) of sodium bromate, 10 ml (174 mmols) of acetic acidand 10 ml of water were charged, and then the resultant mixture wasstirred at room temperature for 24 hours. Along with the progress of thereaction, a small amount of bromine was produced and the temperature ofthe reaction solution was raised to 30° C. After the completion of thereaction, bromine completely disappeared.

With respect to the components in the reaction solution, an area ratioas determined by gas chromatography of benzaldehyde was 91.7% and thatof benzyl alcohol was 5.1%. Using n-tridecane as an internal standardsubstance, quantitative analysis was conducted by gas chromatography(GC). As a result, yield of benzaldehyde as the intended product of thisreaction was 87.6%.

<GC Conditions>

GC analytical conditions used in this example are as follows.

Apparatus: mfd. by Shimadzu Corporation (trade name: GC9-AM)

Column: mfd. by Chemicals Evaluation and Research Institute, Japan(trade name: G-100, 1.0 μm in coating layer thickness×1.2 mm in innerdiameter×20 m in length)

Injection temperature: 280° C.

Carrier gas: Nitrogen gas (20 ml/min)

Detector: FID

Measuring and determination apparatus: mfd. by Shimadzu Corporation(trade name: Chromatopak CR-8A)

Oven temperature conditions: Oven initial temperature: 180° C.; heatingat 10° C./min for 10 minutes; after reaching 280° C., maintaining at thesame temperature

Example 2 (An Embodiment of the Invention Described in the AboveEmbodiment [1]): Production of o-nitrobenzaldehyde

In a 300 ml three-necked flask equipped with a mechanical stirrer, areflux condenser and a thermometer, 61.2 g (400 mmols) of o-nitrobenzylalcohol, 20 g (135 mmols) of sodium bromate, 100 ml (1.74 mols) ofacetic acid and 50 ml of water were charged, and then the resultantmixture was stirred at 50° C. for 3 hours. Along with the progress ofthe reaction, a small amount of bromine was produced and the temperatureof the reaction solution was raised to 68° C. After the stirring of themixture at 90° C. for one hour, 10 g (68 mmols) of sodium bromate wasadded threto, and then the mixture was stirred at 70° C. for one hourand further stirred at 90° C. for one hour.

With respect to the components in the reaction solution, the intendedo-nitrobenzaldehyde was produced in an area ratio, as determined by gaschromatography in the same manner as in Example 1, of 82.2%. It wasconfirmed that the reaction smoothly proceeds by the process accordingto the present invention even in case of a raw material benzyl compoundwherein R′ is an electron-withdrawing group such as nitro group.

Example 3 (An Embodiment of the Invention Described in the AboveEmbodiment [1]): Production of m-methoxybenzaldehyde

In a 15 ml test tube type reaction vessel equipped with a magneticstirrer and a reflux condenser, 0.55 g (4 mmols) of m-methoxybenzylalcohol, 0.18 g (1.2 mmols) of sodium bromate and 2 ml (34.8 mmols) ofacetic acid were charged, and then the resultant mixture was stirred at90° C. for 1.5 hours. Along with the progress of the reaction, a smallamount of bromine was produced. After the completion of the reaction,bromine completely disappeared.

With respect to the components in the reaction solution, the intendedm-methoxybenzaldehyde was produced in an area ratio, as determined bygas chromatography, of 35.2% and 11.7% of m-methoxybenzyl alcohol as araw material was remained. It was confirmed that the reaction proceedsby the process according to the present invention even in case of a rawmaterial benzyl compound wherein R′ is an electron-donating group suchas methoxy group.

Example 4 (An Embodiment of the Invention Described in the AboveEmbodiment [1]): Production of Benzaldehyde

In the same manner as in Example 3, the operation was conducted, exceptthat 0.43 g (4 mmols) of benzyl alcohol was used in place ofm-methoxybenzyl alcohol and 0.39 g (2 mmols) of sodium bromitetrihydrate was used in place of sodium bromate, and also the mixture wasstirred at 50° C. for 4 hours. With respect to the components in thereaction solution, the intended benzaldehyde was produced in an arearatio, as determined by gas chromatography, of 93.5%.

Example 5 (An Embodiment of the Invention Described in the AboveEmbodiment [1]): Production of Benzaldehyde

In the same manner as in Example 3, the operation was conducted, exceptthat 0.43 g (4 mmols) of benzyl alcohol was used in place ofm-methoxybenzyl alcohol and 2 ml (26.8 mmols) of propionic acid was usedin place of acetic acid, and also the mixture was stirred at 80° C. for2.5 hours. With respect to the components in the reaction solution, theintended benzaldehyde was produced in an area ratio, as determined bygas chromatography, of 90.0%.

Example 6 (An Embodiment of the Invention Described in the AboveEmbodiment [1]): Production of o-nitrobenzaldehyde

In the same manner as in Example 3, the operation was conducted, exceptthat 0.67 g (4 mmols) of o-nitrobenzyl methyl ether was used in place ofm-methoxybenzyl alcohol and also 0.2 g (1.35 mmols) of sodium bromatewas used. With respect to the components in the reaction solution, theintended o-nitrobenzaldehyde was produced in an area ratio, asdetermined by gas chromatography, of 53.6% and 38.6% of o-nitrobenzylmethyl ether as a raw material was remained.

Example 7 (An Embodiment of the Invention Described in the AboveEmbodiment [1]): Production of o-nitrobenzaldehyde

In the same manner as in Example 3, the operation was conducted, exceptthat 0.61 g (4 mmols) of o-nitrobenzyl alcohol was used in place ofm-methoxybenzyl alcohol and 2 ml of water and one drop of 47% bromicacid were used in place of 2 ml of acetic acid. With respect to thecomponents in the reaction solution, the intended o-nitrobenzaldehydewas produced in an area ratio, as determined by gas chromatography, of75.2% and 24.2% of o-nitrobenzyl alcohol as a raw material was remained.

Example 8 (An Embodiment of the Invention Described in the AboveEmbodiment [1]): Production of Benzaldehyde

In the same manner as in Example 3, the operation was conducted, exceptthat 0.43 g (4 mmols) of benzyl alcohol was used in place ofm-methoxybenzyl alcohol and 1 ml (17.4 mmols) of acetic acid was used inplace of 2 ml of acetic acid, and also 2 ml of dimethyl formamide and0.2 g (1.35 mmols) of sodium bromate were used. With respect to thecomponents in the reaction solution, the intended benzaldehyde wasproduced in an area ratio, as determined by gas chromatography, of92.6%.

Example 9 (An Embodiment of the Invention Described in the AboveEmbodiment [1]): Production of Benzaldehyde

In the same manner as in Example 8, the operation was conducted, exceptthat 2 ml of propylene carbonate was used in place of 2 ml of dimethylformamide. With respect to the components in the reaction solution, theintended benzaldehyde was produced in an area ratio, as determined bygas chromatography, of 93.4%.

Example 10 (An Embodiment of the Invention Described in the AboveEmbodiment [1]): Production of p-chlorobenzaldehyde

In the same manner as in Example 3, the operation was conducted, exceptthat 0.63 g (4 mmols) of p-chlorobenzyl methyl ether was used in placeof m-methoxybenzyl alcohol and also 0.2 g (1.35 mmols) of sodium bromatewas used. With respect to the components in the reaction solution, theintended p-chlorobenzaldehyde was produced in an area ratio, asdetermined by gas chromatography, of 91.0%.

Example 11 (An Embodiment of the Invention Described in the AboveEmbodiment [1]): Production of 4,4′-bisformylbiphenyl

In the same manner as in Example 3, the operation was conducted, exceptthat 0.53 g (2 mmols) of bismethoxymethylbiphenyl was used in place ofm-methoxybenzyl alcohol and also 0.2 g (1.35 mmols) of sodium bromatewas used. With respect to the components in the reaction solution,4,4′-bisformylbiphenyl was produced in an area ratio, as determined bygas chromatography, of 93.3% and 6.7% of bismethoxymethylbiphenyl as araw material was remained.

Example 12 (An Embodiment of the Invention Described in the AboveEmbodiment [1]): Production of o-phthalaldehyde

In the same manner as in Example 3, the operation was conducted, exceptthat 0.39 g (2 mmols) of o-xylylene glycol diethyl ether was used inplace of m-methoxybenzyl alcohol and also 0.2 g (1.35 mmols) of sodiumbromate was used. With respect to the components in the reactionsolution, the intended o-phthalaldehyde was produced in an area ratio,as determined by gas chromatography, of 32.0% ando-ethoxymethylbenzaldehyde as a product at the intermediate stage(compound in which only one among two ethoxymethyl groups in a moleculeof the raw material was replaced by a formyl group) was produced in anarea ratio of 30.1%.

Example 13 (An Embodiment of the Invention Described in the AboveEmbodiment [1]): Production of p-phthalaldehyde

In the same manner as in Example 3, the operation was conducted, exceptthat 0.55 g (4 mmols) of p-xylylene glycol was used in place ofm-methoxybenzyl alcohol and 1 ml (17.4 mmols) of acetic acid was used inplace of 2 ml of acetic acid, and also 1 ml of water and 0.4 g (2.7mmols) of sodium bromate were used. With respect to the components inthe reaction solution, the intended p-phthalaldehyde was produced in anarea ratio, as determined by gas chromatography, of 56.0% andp-hydroxymethylbenzaldehyde as a product at the intermediate stage(compound in which only one among two hydroxymethyl groups in a moleculeof the raw material was replaced by a formyl group) was produced in anarea ratio of 28.6%.

Example 14 (An Embodiment of the Invention Described in the AboveEmbodiment [1]): Production of Benzaldehyde

In the same manner as in Example 3, the operation was conducted, exceptthat 0.43 g (4 mmols) of benzyl alcohol was used in place ofm-methoxybenzyl alcohol and 0.23 g (1.35 mmols) of potassium bromate wasused in place of sodium bromate. With respect to the components in thereaction solution, the intended benzaldehyde was produced in an arearatio, as determined by gas chromatography, of 90.0%.

Example 15 (An Embodiment of the Invention Described in the AboveEmbodiment [1]): Production of Benzaldehyde

In a 50 ml three-necked flask equipped with a magnetic stirrer, a refluxcondenser and a thermometer, 21.6 g (200 mmols) of benzyl alcohol, 10.0g (67 mmols) of sodium bromate and 20 ml (348 mmols) of acetic acid werecharged, and then the resultant mixture was stirred at 75° C. for 8hours. With the processing of the reaction, a small amount of brominewas produced and the temperature of the reaction solution was raised to80° C. After the completion of the reaction, bromine completelydisappeared. The reaction solution was cooled to room temperature and100 ml of water was added. Under cooling in an ice bath, an aqueous 24%sodium hydroxide solution was added by several portions so as not toraise the liquid temperature until the pH is adjusted to 11 or higher.The resulting product was extracted in turn with 100 ml of ether and 50ml of ether, and then the ether phase was washed with saturated saline.The ether phase was dried over anhydrous sodium sulfate and the solventwas distilled off under reduced pressure to obtain 19.1 g of an oil.With respect to the components in the oil, the intended benzaldehyde wasproduced in an area ratio, as determined by gas chromatography, of89.4%. This oil was purified by distillation under reduced pressure [112to 115° C./13.33 KPa (100 mmHg)] to obtain 13.6 g of benzaldehyde.Isolation yield: 64%.

Example 16 (An Embodiment of the Invention Described in the AboveEmbodiment [1]): Production of p-chlorobenzaldehyde

In a 100 ml four-necked flask equipped with a magnetic stirrer, a refluxcondenser and a thermometer, 31.3 g (200 mmols) of p-chlorobenzyl methylether, 10.0 g (67 mmols) of sodium bromate and 40 ml (696 mmols) ofacetic acid were charged, and then the resultant mixture was stirred at75° C. for 8 hours. With the processing of the reaction, a small amountof bromine was produced and the temperature of the reaction solution wasraised to 80° C. After the completion of the reaction, brominecompletely disappeared. After recovering 28 m of acetic acid underreduced pressure, the resulting reaction solution was cooled to roomtemperature and 100 ml of water was added. An aqueous 24% sodiumhydroxide solution was added by several portions so as not to raise theliquid temperature until the pH is adjusted to 11 or higher. Theresulting product was extracted twice with 100 ml of ethyl acetate andthe ethyl acetate phase was washed with saturated saline. The ethylacetate phase was dried over anhydrous sodium sulfate and the solventwas distilled off under reduced pressure to obtain 29.0 g of a solid.With respect to the components in the solid, the intendedp-chlorobenzaldehyde was produced in an area ratio, as determined by gaschromatography, of 89.2%.

Comparative Example 1 Production of Benzaldehyde

In the same manner as in Example 4, the operation was conducted, exceptthat 0.43 g (4 mmols) of benzyl alcohol was used in place ofm-methoxybenzyl alcohol and 2 ml of dimethyl formamide in place of 2 mlof acetic acid and 0.2 g (1.35 mmols) of sodium bromate were used. Withrespect to the components in the reaction solution, an area ratio asdetermined by gas chromatography of the intended benzaldehyde was 1.3%and that of a raw material benzyl alcohol was 98.7%.

Comparative Example 2 Production of Benzaldehyde

In the same manner as in Example 4, the operation was conducted, exceptthat 0.43 g (4 mmols) of benzyl alcohol was used in place ofm-methoxybenzyl alcohol and 1.8 ml of toluene and 0.2 ml (3.5 mmols) ofacetic acid were used in place of 2 ml of acetic acid, and also 0.2 g(1.35 mmols) of sodium bromate was used. With respect to the componentsin the reaction solution, an area ratio as determined by gaschromatography of the intended benzaldehyde was 2.2% and that of a rawmaterial benzyl alcohol was 96.5%.

Comparative Example 3 Production of Benzaldehyde

In the same manner as in Example 4, the operation was conducted, exceptthat 0.43 g (4 mmols) of benzyl alcohol was used in place ofm-methoxybenzyl alcohol and 2 ml of water in place of 2 ml of aceticacid and 0.2 g (1.35 mmols) of sodium bromate were used. With respect tothe components in the reaction solution, an area ratio as determined bygas chromatography of the intended benzaldehyde was 1.4% and that of araw material benzyl alcohol was 97.9%.

Comparative Example 4 Production of Benzaldehyde

In the same manner as in Example 4, the operation was conducted, exceptthat 0.43 g (4 mmols) of benzyl alcohol was used in place ofm-methoxybenzyl alcohol and 1 ml (17.4 mmols) of acetic acid was used inplace of 2 ml of acetic acid, and also 1 ml of water and 0.14 g (1.35mmols) of sodium chlorate was used in place of sodium bromate. Withrespect to the components in the reaction solution, an area ratio asdetermined by gas chromatography of the intended benzaldehyde was 1.6%,that of benzyl alcohol was 77.9% and that of benzyl acetate was 20.5%.

Comparative Example 5 Production of Benzaldehyde

[Method Described in J. Chem. Research(s), pp. 100 (1998)]

In a 15 ml test tube type reaction vessel equipped with a magneticstirrer and a reflux condenser, 0.43 g (4 mmols) of benzyl alcohol, 0.6g (4 mmols) of sodium bromate, 0.32 g (6 mmols) of ammonium chloride,5.6 ml of acetonitrile and 2.4 ml of water were charged, and then theresultant mixture was stirred at 80° C. for one hour. After 20 minutes,bumping occurred and bromine was vigorously produced. After thecompletion of the reaction, bromine completely disappeared. With respectto the components in the reaction solution, an area ratio as determinedby gas chromatography of the intended benzaldehyde was 12.2%, that of araw material benzyl alcohol was 36.1%, and that of benzoic acid was36.2%.

Example 17 Production of o-iodobenzaldehyde

In a 25 ml Kjeldahl flask equipped with a magnetic stirrer and a refluxcondenser, 2.30 g (9.8 mmols) of o-iodobenzyl alcohol and 5 ml of (87mmols) of acetic acid were charged and an aqueous solution prepared bydissolving 0.50 g (3.33 mmols) of sodium bromate in 3 ml of water wasadded dropwise over 2 hours under stirring. After the completion ofdropwise addition, stirring was conducted at 75° C. for 3 hours. Withrespect to the components in the reaction solution, an area ratio asdetermined by gas chromatography of the intended o-iodobenzaldehyde was99.9% or more. It was confirmed by GS-MS that a molecular ion peak is232.

Example 18 Production of o-methylbenzaldehyde

In a 100 ml four-necked flask equipped with a magnetic stirrer, a refluxcondenser and a thermometer, 12.2 g (100 mmols) of o-methylbenzylalcohol and 20 ml of (333 mmols) of acetic acid were charged and heatedto 80° C. An aqueous solution prepared by dissolving 5.0 g (33 mmols) ofsodium bromate in 20 ml of water was added dropwise over one hours so asnot to raise the temperature in the system to 90° C. or higher. Afterthe stirring of the mixture for one hour, 0.2 g (1.35 mmols) of sodiumbromate was further added, and then the mixture was stirred for one houruntil a red color of bromine disappears. An aqueous sodium carbonatesolution was added to the system until the system is alkalified,followed by extraction twice with 100 ml of ether. The ether phase waswashed with saturated saline and the solvent was distilled off underreduced pressure to obtain 12.5 g of an oil. The resulting oil waspurified by silica gel column chromatography (ethylacetate:n-hexane=1:4) to obtain 11.8 g of o-methylbenzaldehyde. Yield:98.3%. It was confirmed by GS-MS that a molecular ion peak is 120.

Example 19 Production of 2,5-dichlorobenzaldehyde

In a 50 ml three-necked flask equipped with a magnetic stirrer, a refluxcondenser and a thermometer, 7.08 g (40 mmols) of 2,5-dichlorobenzylalcohol and 10 ml of (166 mmols) of acetic acid were charged, followedby heating to 75° C. An aqueous solution prepared by dissolving 2.0 g(13.3 mmols) of sodium bromate in 8 ml of water was added dropwise over2 hours, and then the mixture was stirred at 75° C. for 3 hours. Anaqueous 5% sodium hydroxide solution was added to the system until thesystem is alkalified, followed by extraction with 200 ml ofdichloromethane. The oil phase was washed in turn with water andsaturated saline, and the solvent was distilled off under reducedpressure to obtain 6.8 g of an oil. The resulting oil was purified bysilica gel column chromatography (ethyl acetate:n-hexane=1:4) to obtain5.8 g of 2,5-dichlorobenzaldehyde. Yield: 82.9.

Example 20 Production of 4,4′-bisformylbiphenyl

In a 50 ml three-necked flask equipped with a magnetic stirrer, a refluxcondenser and a thermometer, 4.28 g (20 mmols) of4,4′-bishydroxymethylbiphenyl and 10 ml of (166 mmols) of acetic acidwere charged, followed by heating to 75° C. An aqueous solution preparedby dissolving 2.04 g (13.5 mmols) of sodium bromate in 10 ml of waterwas added dropwise, and then the mixture was stirred at 75° C. until acolor of bromine disappears. To the system, 50 ml of water was addedand, after filtration, the resulting substance was dried to obtain 4.25g of 4,4′-bisformylbiphenyl as a white crystal. Yield: 99.9%. It wasconfirmed by GS-MS that a molecular ion peak is 209.

INDUSTRIAL APPLICABILITY

As described above, according to the present invention, a novel methodfor industrial production of an aromatic aldehyde compound is provided.

According to the process of the present invention, an easily availablebenzyl compound (raw material benzyl compound) represented by a generalformula (1) can be used as a raw material and the intended aromaticaldehyde compound can be produced by a simple operation in highselectivity without using an expensive catalyst or transition metal.Furthermore, since a harmful waste derived from the catalyst ortransition metal is not produced in the process according to the presentinvention, a waste treatment can be easily conducted, and thus theprocess according to the present invention is environmentally friendlyand is industrially useful.

1. A process for producing an aromatic aldehyde compound represented by a general formula (3):

(wherein R′ and n are as defined below), comprising: reacting a benzyl compound represented by a general formula (1):

(wherein R represents a hydrogen atom or an alkyl group, n represents an integer of 1 to 6, and R′ may be the same or different and each independently represents a hydrogen atom, an alkyl group, a hydroxyl group, an alkoxy group, a hydroxyalkyl group, an alkoxyalkyl group, a haloalkyl group, a carboxyl group or a metal salt thereof, an alkoxycarbonyl group, a halogen atom, a nitro group, an amino group, an alkylamino group, an alkylcarbonylamino group, a cyano group, a formyl group, an alkylcarbonyl group, or a phenyl group which may have a substituent), with an oxy-compound of bromine represented by a general formula (2): MBrO_(m)  (2) (wherein M represents a hydrogen atom or a metal atom, and m represents an integer of 1 to 3) in the presence of an acid catalyst.
 2. A process for producing an aromatic aldehyde compound according to claim 1, wherein, in the benzyl compound represented by a general formula (1), all R′(s) are hydrogen atoms or at least one of R′(s) is an electron-withdrawing group.
 3. A process for producing an aromatic aldehyde compound according to claim 1, wherein, in the benzyl compound represented by a general formula (1), all R′(s) are hydrogen atoms or at least one of R′(s) is at least one of a nitro group, a chloro group and a hydroxymethyl group.
 4. A process for producing an aromatic aldehyde compound according to any one of claims 1 to 3, wherein the oxy-compound of bromine represented by a general formula (2) is bromic acid, bromate or bromite.
 5. A process for producing an aromatic aldehyde compound according to any one of claims 1 to 3, wherein the acid catalyst is an organic carboxylic acid. 